Apolipoprotein A-IV enhances cholecystokinnin secretion.
Apolipoprotein A-IV enhances cholecystokinnin secretion.
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DOI：
10.1016/j.physbeh.2018.01.019
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发表时间：
2018-05-01
影响因子：
2.9
通讯作者：
Lo CC
中科院分区：
文献类型：
--
作者：
Zhan J;Weng J;Hunt BG;Sean Davidson W;Liu M;Lo CC
胆囊收缩素（cholestokinin，CCK）和载脂蛋白A-IV（apolipoproteinA-IV，ApoA-IV）是调节能量平衡的重要胃肠肽。在饮食脂质输注期间，淋巴ApoA-IV和血浆CCK分泌通过乳糜微粒形成依赖性途径介导。鉴于它们作为饱腹蛋白的相似作用，本研究探讨了这两种肽在其功能中如何相互作用。具体而言，本研究试图了解ApoA-IV如何调节CCK分泌。为此，在一系列饲养条件下比较了ApoA-IV敲除（ApoA-IV-KO）和野生型（WT）小鼠小肠中的Cck基因表达。当喂食普通饲料或高脂饮食（HFD）时，与WT小鼠相比，ApoA-IV-KO小鼠十二指肠中Cck转录物的基础水平显著降低。此外，经口灌胃脂质混合物后，ApoA-IV-KO小鼠十二指肠中的Cck基因表达相对于WT小鼠中观察到的变化显著降低。为了确定ApoA-IV调节Cck基因表达的机制，用预先设计的小鼠溶血磷脂酸受体5（LPAR 5）小干扰RNA（siRNA）转染STC-1细胞以敲低Lpar 5基因表达。在这项体外研究中，小鼠重组ApoA-IV蛋白增加了肠内分泌STC-1细胞中Cck基因的表达，并刺激了STC-1细胞中CCK的释放。然而，当Lpar 5在STC-1细胞中被敲低时，CCK蛋白和Cck表达水平减弱。总之，这些观察结果表明，膳食脂质诱导的ApoA-IV与十二指肠中的CCK合成相关，并且ApoA-IV蛋白通过激活LPAR 5依赖性途径直接增强CCK释放。
Cholecystokinin (CCK) and apolipoprotein A-IV (ApoA-IV) are gastrointestinal peptides that play an important role in controlling energy homeostasis. Lymphatic ApoA-IV and plasma CCK secretion are mediated via a chylomicron formation-dependent pathway during a dietary lipid infusion. Given their similar roles as satiating proteins, the present study examines how the two peptides interact in their function. Specifically, this study sought to understand how ApoA-IV regulates CCK secretion. For this purpose, Cck gene expression in the small intestines of ApoA-IV knockout (ApoA-IV-KO) and wild-type (WT) mice were compared under an array of feeding conditions. When fed with a chow or high-fat diet (HFD), basal levels of Cck transcripts were significantly reduced in the duodenum of ApoA-IV-KO mice compared to WT mice. Furthermore, after an oral gavage of a lipid mixture, Cck gene expression in the duodenum was significantly reduced in ApoA-IV-KO mice relative to the change seen in WT mice. To determine the mechanism by which ApoA-IV modulates Cck gene expression, STC-1 cells were transfected with predesigned mouse lysophosphatidic acid receptor 5 (LPAR5) small interfering RNA (siRNA) to knockdown Lpar5 gene expression. In this in-vitro study, mouse recombinant ApoA-IV protein increased Cck gene expression in enteroendocrine STC-1 cells and stimulated CCK release from the STC-1 cells. However, the levels of CCK protein and Cck expression were attenuated when Lpar5 was knocked down in the STC-1 cells. Together these observations suggest that dietary lipid-induced ApoA-IV is associated with Cck synthesis in the duodenum and that ApoA-IV protein directly enhances CCK release through the activation of a LPAR5-dependent pathway.
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影响因子：
15.9
作者：
Kahn, BB;Flier, JS
通讯作者：
Flier, JS
影响因子：
6.1
作者：
Foltz, Martin;Ansems, Patrick;Gerhardtt, Cindy C.
通讯作者：
Gerhardtt, Cindy C.
影响因子：
--
作者：
FUJIMOTO, K;CARDELLI, JA;TSO, P
通讯作者：
TSO, P
影响因子：
5.5
作者：
McLaughlin, JT;Lomax, RB;Warhurst, G
通讯作者：
Warhurst, G
DOI：
10.1037/h0034870
发表时间：
1973-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
GIBBS, J;YOUNG, RC;SMITH, GP
通讯作者：
SMITH, GP